M Antibiotic Stewardship Program Experience in a Training and Research Hospital Original Research

(1)

Antibiotic Stewardship Program Experience in a Training and Research Hospital

M

icroorganisms with multiple antibiotic resistanc- es are an important public health problem, which has led to an increase in morbidity, mortality, and health

expenditures. The Infectious Diseases Society of Ameri- ca (IDSA) has been the first to introduce the appropriate antibiotic usage guideline in 1988 against antibiotic re- Objectives: Antibiotic Stewardship Programs (ASP) have been developed for the spread of rational antibiotic use. Our hospital is one of the first centers where ASP applications were launched in Turkey. In this study, we aimed to share our experience with ASP which has been applied in our hospital since 2013.

Methods: We adapted ASP to our hospital program from Centers for Disease Control and Prevention’s ASP checklist. Revisions on surgical prophylaxis guidelines and practices were performed. Surgical prophylaxis was evaluated from hospital infection surveillance and antibiotic usage by point prevalence surveys. Antibiotic consumption indexes (ACI) were calculated from hospital pharmacy records. Rapid antigen detection test (RADT) for Group A beta-hemolytic streptococcus and influenza rapid antigen test were started to be used. Cumulative antibiotic susceptibility results were prepared annually.

Results: Surgical prophylaxis was started to be administered in the operating room within 60 min of incision. Third-generation cephalosporin usage for surgical prophylaxis could be restricted in all clinics but the duration could only be shortened in neurosurgery and general surgery. There was no statistically significant change in antibiotic usage rates and appropriateness between 2014 and 2018. ACI for the class J01 in adult wards was 80.5 daily defined doses (DDD) per 100 patient days in 2014 and reduced to 64.8 DDD per 100 patient days in 2018. 22.445 pediatric patients presenting with complaints of the upper respiratory tract were evaluated with RADT and 75.1% were treated without antibiotics.

Conclusion: In this global antimicrobial resistance era, all hospitals should have motivated antimicrobial stewardship teams. Each hospital should establish its own stewardship program and often revise it. Improvement in rational antibiotic use is hard to achieve without multidisciplinary involvement.

Keywords: Antibiotic stewardship program; antimicrobial resistance; rational antibiotic use.

Please cite this article as ”Eksi Alp E, Oncul A, Dalgic N, Akgun C, Aktas E, Bayraktar B. Antibiotic Stewardship Program Experience in a Training and Research Hospital. Med Bull Sisli Etfal Hosp 2021;55(2):253–261”.

Emel Eksi Alp,¹ Ahsen Oncul,² Nazan Dalgic,³ Cem Akgun,⁴ Elif Aktas,⁵ Banu Bayraktar⁵

1Department of Pediatric Emergency, University of Health Sciences Istanbul, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

2Department of Infectious Diseases, University of Health Sciences Istanbul, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

3Department of Pediatric Infectious Diseases, University of Health Sciences Istanbul, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

4Department of Neurosurgery, University of Health Sciences Istanbul, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

5Department of Microbiology, University of Health Sciences Istanbul, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

Abstract

DOI: 10.14744/SEMB.2020.96337

Med Bull Sisli Etfal Hosp 2021;55(2):253–261

Address for correspondence: Emel Eksi Alp, MD. Saglik Bilimleri Universitesi Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi Cocuk Acil Servisi, Istanbul, Turkey

Phone: +90 506 441 53 73 E-mail: emel.eksi@gmail.com

Submitted Date: May 06, 2020 Accepted Date: December 02, 2020 Available Online Date: July 02, 2021

OPEN ACCESS This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

Original Research

(2)

sistance. In addition to guidelines, national and interna- tional Antibiotic Stewardship Programs (ASP) have been developed.^[1,2] The term “antimicrobial stewardship” was first used in 1996 in United States by McGowan Jr. and Gerding.^[3] ASP is defined as the action plan which pro- vides the appropriate use of antibiotics when necessary.

[4,5] The main objectives of ASP are to determine the ap-

propriate dosage, route, and duration of treatment, to prevent the spread of microorganisms with multiple drug resistance, to reduce the undesirable effects caused by irrational antibiotic use, and to reduce the high cost rates due to unnecessary antibiotic use.^[1,6,7]

ASPs have been developed and implemented in many countries during the 1990s and 2000s. Our hospital is one of the first centers where ASP applications were launched in Turkey. In this study, we aimed to share and evaluate our experience with ASP which has been applied in our hospital since 2013.

Methods

Our hospital is a tertiary teaching hospital with 798 beds (672 beds for adults and 126 beds for pediatric cases). In this study, we shared our 6 years of experience with the ASP, which was adapted to our hospital from Centers for Disease Control and Prevention (CDC)’s ASP checklist, applied by our Antibiotic Control Team (ACT).^[8] Infection diseases specialist (IDS), clinical microbiologist, vice chancel- lor, chief pharmacist, clinical pharmacist, general surgeon, internal medicine specialist, anesthesiologist and reani- mation specialist, infection control nurse, and Information Technologies expert took part in the team. The ACT made its first meeting in October 8, 2013, and continued to con- vene once a month or earlier. Figure 1 shows the low-hanging fruits and plan of our ASP. Physicians from certain clinics were invited to ACT meetings when a problem was detect- ed about the antibiotic usage.

Surgical Prophylaxis

First, studies on surgical prophylaxis and treatment protocols were performed by ACT. Surgical prophylaxis guideline of our hospital was renewed in collaboration with surgeons and was made easily visible through our hospital website institutional portal. Two different options such as “prophylactic” and “treatment” were submitted for electronic antibiotic orders to check up on the concept of prophylaxis and to question the purpose of giving antibiotics on a daily basis. To restrict ceftriaxone consumption, hospital information system was rearranged for the approval on the 1^st day instead of the 3^rd day by IDS. The major changes in prophylaxis guidelines were offering cefuroxime instead of cefazolin in urologic surgeries and

ampicillin sulbactam in biliary surgeries, if needed. Ce- fazolin was the choice for most clean and clean-contaminated surgeries.

It was observed that patients were brought to the operating room after surgical prophylaxis was performed in the wards. Urology Clinic was selected to examine the period between prophylactic antibiotic administration and incision, and it was found to be longer than 2 h in some cases.

To achieve standardization, all surgical prophylaxis were started to be administered by the anesthesia team in the operating room within 60 min before surgical incision.

Global guidelines for the prevention of surgical site infection point out prolonged antibiotic prophylaxis exceed- ed 24 h after surgery has no advantage in surgical site infections.^[9] We examined appropriate surgical antibiotic prophylaxis duration times and prophylactic antibiotic choices by previously determined surgical wards in 2014 and 2018 from surgical site infection surveillance data.

Figure 1. Our ASP action plan.

ACI: Antibiotic consumption index; URTI: Upper respiratory tract infection.

ASP action plan

In-patient Out-patient

Surgical prophylaxis

• Antibiotic choice

• Administiration time

• Prophylaxis duration

• Reduction of antibiotic use in viral URTIs

• Utilization of rapid antigen test for group A beta hemolytic streptococcus and Influenza antigen tests

• Banners about rational drug and antibiotic use Treatment

• ACI surveys

• Restriction of broad spectrum antibiotics/

ID approval

• Discontinuation of rifampicin ampoules for wound care

Microbiology and culture sampling

• Preparation of cumulative antibiotic succeptibility results

• Education on accurate sampling

• Reduction of surgical site infections

(3)

The clinics were chosen in terms of surgical site infection risk and the surgeries that we could exclude contaminated or dirty operations. Comparative surgical prophylaxis data with the previous months were given to the clinical chiefs, quarterly.

Antibiotic Usage

Principles have been developed by the World Health Organization (WHO) for the prevention of inappropriate prescription of antibiotics.^[10] Irrational antibiotic use is also serious public health problem which affects our country, too. The Ministry of Health in Turkey launched a nationwide antibiotic restriction program in Febru- ary 2003. According to this program; anti-pseudomo- nal beta-lactamase inhibitors, intravenous third- and fourth-generation cephalosporins, carbapenems, parenteral quinolones, parenteral antifungals, anti-Methicil- lin-resistant Staphylococcus aureus (MRSA) agents (van- comycin, linezolid, and daptomycin), and polymyxins (colistin), new generation antibiotics such as tigecycline can only be used with IDS approval through a computer- ized pre-authorization system.

The current antibiotic usage and antibiotic applications in our hospital were discussed in the context of the guidelines.^[11,12] Rearrangements have been made in the hospital information system related to antibiotic practices. A “Con- trolled Antibiotic Request Form” was created for antibiotic requests which need IDS approval. The differences between antibiotic usage rates and appropriateness among surgical and medical adult wards were evaluated by point prevalence surveys (PPS) in February 26, 2014 and Janu- ary 23, 2018. Antibiotic consumption indexes (ACIs) were retrieved from hospital pharmacy records. ACIs of adult clinics were started to be analyzed to follow the results of rearrangements in treatment protocols and to compare our data with other hospitals. For this purpose, An- atomical Therapeutic Chemical (ATC) Classification/Daily Defined Doses (DDD) system, which is recommended by the WHO, was used.^[13] ABC Calc version 3.1 was used for ACI calculation on a Microsoft Excel® application. This application converted the number of dispensed units (vials, pills, capsules, or bottles) into the number of DDD and then to the number of DDD/100 PD, as recommended by the WHO, following the 2006 version of ATC/DDD classification. The old DDD were used for 2018 calculation to compare the data with 2014.

Studies suggest that antibiotic use in viral upper respiratory tract infections is the most common cause of antibiotic misuse in out-patient clinics.^[14-16] We aimed to reduce antibiotic prescribing rates in viral upper respiratory tract infections, mainly in emergency clinics. Thus, rapid antigen

detection test (RADT) for Group A beta-hemolytic streptococcus (GABHS) and influenza rapid antigen test (IRAT) were started to be used. Intramuscular benzathine peni- cillin was supplied from the hospital pharmacy to ensure the application of antibiotherapy for patients infected with GABHS. Antibiotic prescribing rates in acute tonsillopharyngitis were evaluated after RADT use.

Rifampicin

Rifampicin is a valuable drug for the treatment of tuber- culosis.^[17] Rifampicin ampoules were frequently used in wound care in Physical Therapy and Rehabilitation, Neu- rosurgery, Orthopedics, and Plastic Surgery Clinics in our hospital. Interviews were conducted with these clinics to prevent local use of rifampicin ampoules for wound care. A local wound care guide prepared by ACT with the contribu- tion of these departments.

Microbiology and Culture Sampling

Cumulative local antibiotic susceptibility results were prepared annually according to guidelines.^[18] These reports, which are guiding in empirical treatment, were shared on the hospital institutional portal and were announced to all doctors by e-mail.

Education on accurate sampling for cultures was given by Microbiology and Infectious Diseases Clinics to the related clinics. To reduce blood culture contamination rates, chlor- hexidine and alcohol-containing wipes were put into the blood culture kits and given to the clinics (except for babies under 2 months).

In case of positive blood culture results, information was given to physicians by Microbiology Clinic.

Surgical Site Infections

In line with the recommendations renewed in November 2016 by the WHO,^[9] posters were created and hung in visible places in operating rooms. Guidelines for the treatment of complicated intra-abdominal infections have been prepared and shared with Adult and Pediatric Gastroenterolo- gy Clinics.

Data Analysis and Ethics Approval

All statistical analyses were done using IBM SPSS Statis- tics, version 21.0. According to distribution of data, Stu- dent t or Mann–Whitney U-test were used. Chi-square and Fisher’s exact tests were used for categorical variables as appropriate. All analyses were considered significant at p<0.05. The study was assessed by the Regional Ethical Review Board in Sisli, Turkey on 16, April 2019, registration number 2347.

(4)

Results

Surgical Prophylaxis

Significant differences were observed in surgical prophylaxis applications through our ASP. When the clinics were evaluated separately, prophylactic ceftriaxone usage decreased from 49.3% in 2014 to 11.4% in 2018 in General Surgery Clin- ic; 7.8% to zero in Neurosurgery; and 30% to zero in Urology Clinic (p<0.01). In general surgery, this may be due to the change in surveyed operations, but Urology and Neurosur- gery Clinics fully accepted the advised prophylactic agents.

In Urology Clinic, as second-generation cephalosporins do not need IDS approval in our country, we could not achieve the appropriate duration and nearly all patients received

prolonged antimicrobial prophylaxis. Furthermore, the Gy- necology Clinic started to use more prolonged prophylaxis; but we could not be successful in reducing unrestricted first-generation cefalosporin use although we gave multiple education and feedbacks. The Orthopedics and Traumatol- ogy Clinic changed their protocol and started to give ampicillin sulbactam following cefazolin. We could be able to restrict WHO watch group antibiotics for surgical prophylaxis and shorten the duration of surgical prophylaxis in neurosurgery and general surgery. Changes of antibiotic choices for surgical prophylaxis in various clinics in 2014 and 2018 are summarized in Table 1. Appropriate surgical antibiotic prophylaxis duration times by surgical wards and by year of evaluation 2014 and 2018 are shown in Table 2.

Table 1. Surgical antibiotic prophylaxis – antimicrobial agent, change in years

Clinics -antibiotics 2014 2018 P

n (%) n (%)

Obstetrics and gynecology

Cefazolin 252 (91.6) 326 (87.2) 0.07

Others (mainly metronidazole combination) 23 (8.4) 48 (12.8) Neurosurgery

Cefazolin 302 (93.2) 397 (100) <0.01

Ceftriaxone 22 (7.8) 0

General surgery

Ampicillin sulbactam 108 (41.8) 389 (71.2) <0.01

Cefazolin 23 (8.9) 95 (17.4)

Ceftriaxone 127 (49.3) 62 (11.4)

Urology

Cefazolin 1(1) 0 <0.01

Cefuroxime 83 (69) 128 (100)

Ceftriaxone 36 (30) 0

Orthopedics and traumatology

Cefazolin 262 (100) 219 (100) -

Ampicillin sulbactam* 194 (88.6)

*Prophylaxis continued with ampicillin sulbactam after cefazolin administration. **% means column % in clinic subset.

Table 2. Surgical antibiotic prophylaxis surveillance-duration

Surveyed clinics 2014 2018 P Appropriate duration Prolonged Appropriate duration Prolonged

n % n % n % n %

Obstetrics and gynecology 213 77.5 62 22.5 97 26 277 74 <0.01

Neurosurgery 151 46.6 173 53.4 392 98.7 5 1.3 <0.01

General surgery 107 41.5 151 58.5 296 54.2 250 45.8 <0.01

Orthopedics and traumotology 265 100 0 0 217 52.6 196 47.4 <0.01

Urology 36 30 84 70 4 3 124 97 <0.01

Hospital total surveyed clinics 772 62 470 38 1006 54.3 852 45.7 <0.01 Appropriate duration: Up to 72 h for orthopedic surgery, up to 24 h for others

(5)

Antibiotic Usage

Antibiotic consumption for the ATC class J01 (i.e., antibacterial for systemic use) was 80.5 DDD per 100 patient days in 2014, and 64.8 DDD per 100 patient days in 2018. Table 3 shows the consumption of antimicrobials by ATC groups, expressed as DDD per 100 patient days, in all adult wards, including intensive care units in 2014 and 2018, April to July.

The most used classes were penicillins without antipseudomonal activity combined with beta-lactamase inhibitors (J01CR01, J01CR02, and J01CR04), third-generation cephalosporins (J01DB), and first-generation cephalosporins (J01DC). We could achieve 45% reduction in third-generation cephalosporin consumption and 48% reduction in fluoroquinolone consumption. There were some increases in consumption of tetracyclines (J01AA), second-generation cephalosporins (J01DC), and glycopeptides (J01XA) but these were minor in terms of DDDs. Carbapenem and polymyxin use also decreased by 26% and 58%, respectively, but decrease in polymyxins may be related to temporary shortages in hospital pharmacy.

In surgical wards, antibiotic usage rate was 46.4% (111 of 239 inpatients) in 2014 PPS and 49.6% in 2018 PPS (121 of 244 inpatients) (p=0.49). Approximately in half of the surgi-

cal patients treated with antibiotics, antibiotics were given inappropriately (49 of 111 patients in 2014 PPS; and 54 of 121 patients in 2018 PPS) (p=0.94).

In medical wards, 64 of 216 inpatients were taking antibiotics on the day of 2014 PPS with the rate of 29.6%. Antibi- otic usage rate decreased to 25.4% (47 in 185 inpatients) in 2018 PPS, (p=0.35). Appropriateness was 79.7% (51 in 64 patients) and 87.2% (41 in 47 patients) in 2014 and 2018 PPS, respectively (p=0.29).

In both 2014 and 2018 PPSs, more patients in surgical wards were taking antibiotics (p<0.01) but appropriateness, in terms of compliance with guidelines was higher in medical wards (p<0.01). There was no statistically significant change in antibiotic usage and appropriateness between 2014 and 2018 in both medical and surgical units.

In the PPS conducted in 2014 when the distribution of antibiotic use was evaluated in surgical clinics, it was seen that 66.7% (n=74) of the patients had prophylaxis and 33.3%

(n=37) of them were treated with antibiotics. The most commonly used antibiotics for treatment in surgical clinics were cefazolin (44.1%; n=49), ampicillin-sulbactam (19.8%;

n=22), and ceftriaxone (19.8%; n=22), respectively. In the PPS conducted in 2018, the most commonly used antibi-

Table 3. Antibiotic consumption of all antibacterial for systemic use (J01)in adult wards, 2014 and 2018

Therapeutic group 2014 2018

DDD DDD/100 pd DDD DDD/100 pd

Tetracyclines (J01AA) 112 0.3 445 1

Penicillins with extended spectrum(PES) (J01CA) 189 0.5 344 0.8

Beta-lactamase sensitive penicillins (J01CE) 227 0.6 222.5 0.5

PES without antipseudomonal activity+ 10698 28.15 10337 24.5

beta-lactamase inhibitors (J01CR01, J01CR02, J01CR04)

Antipseudomonal penicillins+ 931.7 2.5 821.4 1.9

beta-lactamase inhibitors (J01CR05)

First-generation cephalosporins (J01DB) 3643 9.6 3456 8.1

Second-generation cephalosporins (J01DC) 231.3 0.6 633.5 1.5

Third-generation cephalosporins (J01DD) 4756.8 12.52 2954.5 6.9

Fourth-generation cephalosporins (J01DE) 24.8 0.07 64.5 0.2

Carbapenems (J01DH) 2862.2 7.5 2361.8 5.5

Sulfamethoxazole and trimethoprim (J01EE01) 42 0.11 488.8 1.1

Macrolides, lincosamides, streptogramins (J01F) 771.3 2.01 936.8 2.2

Aminoglycosides (J01GB) 402.6 1.06 253.4 0.6

Fluoroquinolones (J01MA) 2797.2 7.36 1580.5 3.7

Glycopeptides (J01XA) 288.4 0.8 540.3 1.3

Polymyxins (J01XB) 551 1.45 264.5 0.6

Imidazole derivatives (J01XD) 1519 4 1370.8 3.2

Others 554.7 1.4 601 1.2

Antibiotics for systemic use (total J01) 30602 80.5 27319.4 64.8

DDD: Daily defined dose; pd: Patient day. 2014 pd: 37997 2018 pd: 42595

(6)

otics in surgical clinics were ampicillin-sulbactam (43%;

n=55) and cefazolin (39%; n=50).

When antibiotic appropriateness was evaluated in 2014, antibiotic usage in 35.4% (n=62/175) of medical and surgical patients was evaluated as “inappropriate.” There were more than one reason for inappropriateness in 22 patients.

In all patients receiving antibiotherapy, 10.2% (n=18) considered as unnecessary, 7.4% (n=13) as microbiologically inappropriate, 14.2% (n=25) as pharmacologically inappropriate, and finally as 16% (n=28) as prolonged surgical prophylaxis.

For out-patient antimicrobial stewardship, a total of 22.445 throat samples for RADT and throat culture were collect- ed at the pediatric emergency clinic between November 2014 and April 2018. Bacterial tonsillopharyngitis were diagnosed in 24.9% (n=5591) of these patients and 75.1%

(n=16854) of suspected cases have been treated without

antibiotics. We diagnosed 98.5% (n=5511) of GABHS in a short time such as 30 min with RADT and we applied antibiotherapy. In 2018–2019 influenza season, a total of 628 patients underwent IRAT for influenza-like symptoms. In- fluenza A or B positivity rates were 37.7% (n=237).

Rifampicin

As a result of the cooperation with the related clinics and prepared guidelines, rifampicin ampoule consumption gradually decreased and discontinued within 1 year in local wound care. One hundred-eighty-nine rifampicin ampoules consumed in the quarter of 2014 (between April- June), whereas there were no consumption in 2018.

Microbiology and Culture Sampling

Our local antimicrobial susceptibility profiles were prepared (Table 4). MRSA percentages for 2014–2017 range 13–28% for outpatient, 17–25% for inpatient, and 29–44%

Table 4. Local cumulative antimicrobial susceptibility profiles

Species Antibiotic Susceptibility percentages from 2014 to 2017 (%)

Out-patient In-patient ICU

Escherichia coli CRO 74-75-73-72 70-58-57-55 46-48-58-58

MEM 99-99-99-97 99-99-99-93 100-99-100-100

CIP 76-77-73-72 69-65-63-59 55-55-79-63 GN 85-87-85-84 82-78-77-73 73-74-82-80 AK 99-99-99-97 99-99-98-92 100-99-99-96

Klebsiella pneumoniae CRO 56-66-61-61 48-53-34-52 48-26-42-46

MEM 94-95-97-92 97-88-83-90 94-69-72-79 CIP 74-79-71-67 70-66-49-64 77-40-53-60 GN 81-82-81-78 72-75-66-79 70-41-58-61 AK 96-98-96-90 96-95-89-89 100-82-91-80

Pseudomonas aeruginosa CAZ 80-83-88-87 92-84-83-89 NA

PİP-TAZO 91-82-92-85 96-82-85-85 NA

MEM 87-82-95-90 90-86-87-87 NA

CIP 82-82-85-76 88-81-84-85 NA

GN 81-79-89-84 85-81-88-89 NA

AK 95-95-96-96 97-95-92-90 NA

Acinetobacter baumannii MEM NA 24-18-23-17 7-3-5-2

CIP NA 12-16-23-13 1-3-6-2

GN NA 23-18-30-23 14-6-7-6

AK NA 27-46-32-15 24-30-9-4

TMP-SXT NA 43-43-34-22 16-22-15-22

Staphylococcus aureus CC 93-88-89-90 98-70-86-80 NA-72-81-67

ER 86-82-85-89 89-69-82-80 NA-72-71-67 LZD 98-99-100-100 100-99-100-100 NA-100-98-100

TET 100-100-82-86 100-100-78-85 NA-100-64-63 CIP 100-94-89-97 NA-94-90-97 NA-86-81-72 ICU: Intensive care unit;CRO: Ceftriaxone; MEM: Meropenem; CIP: Ciprofloxacin; GN: Gentamicin; AK: Amikacin; CAZ: Ceftazidime; PIP-TAZO: Piperacillin- Tazobactam; TMP-SXT: Trimethoprim-Sulfamethoxazole; CC: Clindamycin; ER: Erythromycin; LZD: Linezolid; TET: tetracycline; NA: non-applicable, number of Pseudomonas aeruginosa isolates for ICU and Acinetobacter baumannii isolates for out-patient were too low (n<30) to calculate susceptibility percentages.

(7)

for ICU. The PPS in 2014 showed that the rates of collect- ing blood and suspected site cultures were low before be- ginning of antibiotherapy (31.6%; n=60). These rates were 10.8% (n=12) in surgical clinics, 57.8% (n=37) in internal clinics and 73.3% (n=11) in ICUs. Microbiological sampling rate in surgical clinics was significantly lower than medical clinics and ICUs (p<0.05).

Discussion

Turkey has the highest rate of antibiotic consumption among Organization for Economic Co-operation and Devel- opment countries. In 2013, the National Action Plan on Ra- tional Drug Use was developed and implemented to reduce the rate of antibiotic consumption in Turkey.^[19,20] In line with the National Action Plan, we have achieved positive devel- opments after implementation of ASP in our hospital like other countries.^[21,22] Italy and Turkey are both countries with high antimicrobial resistance rates. Barchitta et al. reported antibiotic consumption in Southern Italy for the ATC class J01 (i.e., antibacterial for systemic use) in hospitals to be in the range of 74.2–100.7 DDD per 100 patient days from 2015 to 2017. Our results show similar consumption in 2014 with 80.5 DDD per 100 patient days, while it was found to be reduced to 64.8 DDD/100 patient days in 2018.^[23]

Studies have shown that approximately 30% of antibiotics used in hospitals are misused or unnecessary.^[24] Antimicro- bial resistance may occur due to inappropriate antibiotic use and ASP is shown to affect the use of appropriate antibiotics positively.^[25,26] In a study conducted in China, the rate of antibiotic use was 39.4%, the most commonly used antibiotics were first-generation cephalosporins (19.9%) and ampicillin-sulbactam (19.1%). They found appropriate antibiotic use as 64.2%.^[27] Similar results were obtained in a PPS conducted in our country that included 113 patients in 2018 (rate of antibiotic use was 70.8% and inappropriate antibiotic use was 33.8%).^[28] When the data of our hospital were examined, antibiotic preferences and appropriate antibiotic usage rates of 65.8% (n=125) were also consistent with the literature.

The aim of surgical prophylaxis is to prevent contamination in clean-contaminated and some clean operations un- til the incision is closed. Studies and published guidelines suggest that prophylaxis should be administered within 60 min before the first incision to keep the time minimum between prophylaxis and surgery onset.^[29] ASP is important for optimizing surgical antibiotic prophylaxis duration times. Saied et al. evaluated five surgical hospitals in a before-and-after intervention study. This multicenter pilot intervention study shows that all hospitals showed a significant rise in the optimal duration of surgical prophylaxis

after implementation of ASP.^[30] van Kasteren et al. audited the quality of prophylaxis before and after the intervention.

They found that prolonged prophylaxis was only in 31.4%

cases instead of 46.8% expected cases in 13 Dutch hospitals.^[31] It should be considered that unnecessary prolonged prophylaxis leads to increased cost, infection with resistant bacteria, and undesirable side effects. When we examined our surgical clinics, we could achieve right administration time after implementing ASP in our hospital. We reduced the use of broad spectrum antibiotics, but could not limit the prolonged use of surgical prophylaxis except neurosur- gical and general surgery operations.

As our enterobacteriaceae resistance rates to cefazolin and ampicillin sulbactam were similar, we offered ampicillin sulbactam as an alternative in biliary surgery. World Health organization (WHO) experts are also recommend- ing cefazolin, cefuroxime, and amoxicillin clavulanic acid as first-line prophylactic agents for cholecystectomy in “The Selection and Use of Essential Medicines Report of the 22^nd WHO Expert Committee.^[32]” It is also stated in the report that there is no reason to use ceftriaxone for surgical prophylaxis agent as it belongs to the Essential Medicine List- Watch group and WHO highest-priority, critically important antimicrobials list.^[33,34]

Ceftriaxone does not have additional effect on extended spectrum beta-lactamase producing bacteria and has high risk of selecting resistant bacteria. In a multidisciplinary meeting that we invited Urology Clinic to our ACT about the excessive ceftriaxone use, clinicians stated their con- cerns to use cefazolin as prophylaxis because of its weak effectiveness on Gram-negative agents and a decision of using a second-generation cephalosporin as first-line prophylactic agent for clean-contaminated urologic surgery has been taken. In our results, it’s seen that ceftriaxone use is avoided to be used for urologic surgery and cefuroxime has taken its place. Cefuroxime is also recommended as a first choice agent for urologic surgeries by the WHO expert committee.^[32] Sharma et al. found that surgical prophylaxis protocol with one dose cefuroxime was effective in 89.5%

of patients who underwent clean or clean-contaminated urologic surgery.^[35]

Local cumulative antibiograms are very important for antibiotic stewardship at local level. Physicians’ prior knowledge of local drug resistance rates will support their clinical decision-making and guide the empirical treatment choices. Furthermore, changes about local cumulative antimicrobial susceptibility profiles uncover resistance over time and drug-resistant organisms.^[36-38] Based on the importance of publishing local antibiograms, we have regularly edited our annual local antibiogram data since 2013.

(8)

Upper respiratory tract infections are the most common causes of excessive antibiotic use among outpatients. Diag- nosis of bacterial tonsillopharyngitis should be confirmed by laboratory tests in patients whose signs and symptoms support bacterial etiology. Throat culture is the gold stan- dard method for the diagnosis of bacterial tonsillopharyngitis and RADT is a high-sensitive, quick, cost-effective, and reliable tool for screening bacterial tonsillopharyngitis. As waiting culture results may lead to delay in treatment or may cause antibiotic prescription without evaluation of culture results, we used RADT in addition to throat culture to guide our treatment plan and to take early results.^[39,40]

This study had some limitations. First, due to the changes made in the digitalization stages of our hospital system, data before 2014 could not be reached. Second, we did not have any data on antibiotic prescribing rates before the use of RADT in patients with acute tonsillopharyngitis. Third, we could not analyze any changes about culture sampling rates after implementation of ASP because this data were not analyzed in the PPS conducted in 2018. Fourth, there are no clinical outcomes (i.e., effects on mortality or on clostridium difficile infection incidence) or effects on antibiotic susceptibility profile reported after ASP implementation, only process measures used. Fifth, cost-effectiveness has not been investigated in the studies conducted with ASP in our hospital.

Conclusion

This is one of the first comprehensive studies carried out in accordance with CDC recommendations generated by the ASP for a hospital in Turkey. In this global antimicrobial resistance era, all hospitals should have motivated antimicrobial stewardship teams, determine the low hanging fruits for their institutions and give feedbacks to the prescribing clinicians about their surveillance. Improvement in rational antibiotic use is hard to achieve without multidisciplinary involvement, especially surgeons.

Disclosures

Ethics Committee Approval: The study was assessed by the Regional Ethical Review Board in Sisli, Turkey on 16^th April 2019, registration number 2347.

Peer-review: Externally peer-reviewed.

Conflict of Interest: The authors declare that they have no conflict of interest.

Authorship Contributions: Concept – N.D., E.A.; Design – N.D., E.E.A., A.O.; Supervision – N.D., B.B., C.A.; Materials – N/A; Data col- lection &/or processing – N.D., E.E.A., C.A., A.O.; Analysis and/or in- terpretation – E.E.A., N.D., A.O., B.B.; Literature search – E.E.A., N.D., E.A.; Writing – E.E.A., N.D., A.O.; Critical review – N.D., E.A., B.B., C.A.

References

1. Dellit TH. Summary of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guide- lines for developing an institutional program to enhance antimicrobial stewardship. Infect Dis Clin Pract 2007;15:263–4. [CrossRef]

2. Perozziello A, Routelous C, Charani E, Truel A, Birgand G, Yazdan- panah Y, et al; CEFECA Study Group. Experiences and perspectives of implementing antimicrobial stewardship in five French hospitals: a qualitative study. Int J Antimicrob Agents 2018;51:829–35.

3. McGowan JE Jr, Gerding DN. Does antibiotic restriction prevent resistance? New Horiz 1996;4:370–6.

4. Dyar OJ, Huttner B, Schouten J, Pulcini C; ESGAP (ESCMID Study Group for Antimicrobial stewardshiP). What is antimicrobial stewardship? Clin Microbiol Infect 2017;23:793–8. [CrossRef]

5. Pulcini C, Binda F, Lamkang AS, Trett A, Charani E, Goff DA, et al.

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach.

Clin Microbiol Infect 2019;25:20–5. [CrossRef]

6. Lee KB, Ramirez JA, Collins R, Bucheit J, Sanogo K, Stevens MP. An- timicrobial stewardship practices in Virginia. Am J Infect Control 2017;45:451–2. [CrossRef]

7. Richards DA, Hanson J. Successful antimicrobial stewardship program collaboration. Am J Infect Control 2017;45:19. [CrossRef]

8. Centers for Disease Control and Prevention. Checklist for Core Elements of Hospital Antibiotic Stewardship Programs. Available at: https://www.cdc.gov/antibiotic-use/healthcare/pdfs/checklist.pdf. Accessed May 10, 2019.

9. Leaper DJ, Edmiston CE. World Health Organization: global guidelines for the prevention of surgical site infection. J Hosp In- fect 2017;95:135–6. [CrossRef]

10. Graft-Aikins A, Chalker J, Lee D, Miralles M. Interventions and strategies to improve the use of antimicrobials in developing countries: A review. Available at: https://www.who.int/csr/re- sources/publications/drugresist/Interventions.pdf. Accessed Apr 5, 2021.

11. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/Ameri- can Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27–72. [CrossRef]

12. Özlü T, Bülbül L, Alataş F, Arseven O, Şakar Coşkun A, Çilli A et al.

Diagnosis and Treatment Consensus Report of Community-Ac- quired Pneumonia in Adults. Turk Thorac J 2009;10:3–16.

13. World Health Organization (WHO). ATC/DDD Index. Available at:

https://www.whocc.no/atc_ddd_index. Accessed May 10, 2019.

14. Harnden A, Perera R, Brueggemann AB, Mayon-White R, Crook DW, Thomson A, et al. Respiratory infections for which general practitioners consider prescribing an antibiotic: a prospective study. Arch Dis Child 2007;92:594–7. [CrossRef]

(9)

15. Shlomo V, Adi R, Eliezer K. The knowledge and expectations of parents about the role of antibiotic treatment in upper respiratory tract infection-a survey among parents attending the primary physician with their sick child. BMC Fam Pract 2003;4:20. [CrossRef]

16. Zyoud SH, Abu Taha A, Araj KF, Abahri IA, Sawalha AF, Sweileh WM, et al. Parental knowledge, attitudes and practices regarding antibiotic use for acute upper respiratory tract infections in children:

a cross-sectional study in Palestine. BMC Pediatr 2015;15:176.

17. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. 2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections. J Am Podiatr Med Assoc 2013;103:2–7. [CrossRef]

18. CLSI. Analysis and presentation of cumulative antimicrobial susceptibility test data; approved guideline-4th Edition. CLSI docu- ment M39-A4. Wayne, PA: Clinical and Laboratory Standards Insti- tute; 2014.

19. Versporten A, Bolokhovets G, Ghazaryan L, Abilova V, Pyshnik G, Spasojevic T, et al; WHO/Europe-ESAC Project Group. Antibiotic use in eastern Europe: a cross-national database study in coordi- nation with the WHO Regional Office for Europe. Lancet Infect Dis 2014;14:381–7. [CrossRef]

20. Aksoy M, Alkan A, Isli F. Rational Drug Use Promotional Activities of Ministry of Health. Turkiye Klinikleri J Pharmacol-Special Topics 2015;3:19–26.

21. Skoog G, Struwe J, Cars O, Hanberger H, Odenholt I, Prag M, Skär- lund K, Ulleryd P, Erntell M. Repeated nationwide point-prevalence surveys of antimicrobial use in Swedish hospitals: data for actions 2003-2010. Euro Surveill 2016;21. [CrossRef]

22. Muraki Y, Yagi T, Tsuji Y, Nishimura N, Tanabe M, Niwa T, et al. Japa- nese antimicrobial consumption surveillance: First report on oral and parenteral antimicrobial consumption in Japan (2009-2013).

J Glob Antimicrob Resist 2016;7:19–23. [CrossRef]

23. Barchitta M, Quattrocchi A, Maugeri A, La Rosa MC, La Mastra C, Sessa L, et al. Antibiotic Consumption and Resistance during a 3-Year Period in Sicily, Southern Italy. Int J Environ Res Public Health 2019;16:2253. [CrossRef]

24. Centers for Disease Control and Prevention. Antibiotic use in the United States, 2017: Progress and Opportunities. Available at: https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/

stewardship-report.pdf. Accessed May 7, 2019.

25. Nathwani D, Varghese D, Stephens J, Ansari W, Martin S, Charbon- neau C. Value of hospital antimicrobial stewardship programs [ASPs]: a systematic review. Antimicrob Resist Infect Control 2019;8:35. [CrossRef]

26. Madran B, Keske Ş, Tokça G, Dönmez E, Ferhanoğlu B, Çetiner M, et al. Implementation of an antimicrobial stewardship program for patients with febrile neutropenia. Am J Infect Control 2018;46:420–4. [CrossRef]

27. Qu X, Yin C, Sun X, Huang S, Li C, Dong P, et al. Consumption of antibiotics in Chinese public general tertiary hospitals (2011-

2014): Trends, pattern changes and regional differences. PLoS One 2018;13:e0196668. [CrossRef]

28. Ergül AB, Gökçek İ, Çelik T, Torun YA. Assessment of inappropriate antibiotic use in pediatric patients: Point-prevalence study. Turk Pediatri Ars 2018;53:17–23. [CrossRef]

29. Tarchini G, Liau KH, Solomkin JS. Antimicrobial stewardship in surgery: challenges and opportunities. Clin Infect Dis 2017;64:S112–4.

30. Saied T, Hafez SF, Kandeel A, El-kholy A, Ismail G, Aboushady M, et al. Antimicrobial stewardship to optimize the use of antimicrobials for surgical prophylaxis in Egypt: A multicenter pilot intervention study. Am J Infect Control 2015;43:e67–71. [CrossRef]

31. van Kasteren ME, Mannien J, Kullberg BJ, de Boer AS, Nagelkerke NJ, Ridderhof M, et al. Quality improvement of surgical prophylaxis in Dutch hospitals: evaluation of a multi-site intervention by time series analysis. J Antimicrob Chemother 2005;56:1094–102.

32. World Health Organization (WHO). The selection and use of essential medicines. WHO Technical Report Series 2019. Available at:

https://www.who.int/medicines/publications/essentialmedicines/

UNEDITED_TRS_2019_EC22_Sept.pdf?ua=1. Accessed Apr 6, 2021.

33. World Health Organization (WHO). WHO model list of essential medicines, 20th list. Geneva: World Health Organization; 2017.

Available at: https://www.who.int/medicines/publications/essentialmedicines/en/. Accessed Jan 15, 2019.

34. World Health Organization (WHO). Critically important antimicrobials for human medicine, 5th revision. Available at: https://

www.who.int/foodsafety/publications/antimicrobials-fifth/en/.

Accessed Apr 6, 2021.

35. Sharma AP, Devana SK, Bora GS, Mavuduru RS, Mohan B, Taneja N, et al. Protocol-based perioperative antimicrobial prophylaxis in urologic surgeries: Feasibility and lessons learned. Indian J Urol 2019;35:141–6.

36. Gül M, Seber E. The distribution of the microorganisms that have been isolated from wound and abscesses in consideration of clinics and their antibiotic susceptibility. Sisli Etfal Hastan Tip Bul 2002;36:13–8.

37. Hindler JF, Stelling J. Analysis and presentation of cumulative antibiograms: a new consensus guideline from the Clinical and Laboratory Standards Institute. Clin Infect Dis 2007;44:867–73.

38. Bayraktar B, Pelit S, Bulut ME, Aktaş E. Trend in antibiotic resistance of extended-spectrum beta-lactamase-producing Esch- erichia coli and Klebsiella pneumoniae bloodstream infections.

Sisli Etfal Hastan Tip Bul 2019;53:70–5. [CrossRef]

39. Ekşi Alp E, Dalgıç N, Kına N, Bayraktar B, Öncül A, Aktaş Sepetci E.

The importance of rapid antigen testing for group A streptococ- cal tonsillopharyngitis: A single center experience. J Pediatr Inf 2018;12:93–8. [CrossRef]

40. Hersh AL, Jackson MA, Hicks LA; American Academy of Pediatrics Committee on Infectious Diseases. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics 2013;132:1146–54. [CrossRef]